The invention relates to apparatus and methods for hyperpolarizing noble gases. Specifically, the invention relates to methods and apparatus for producing significant quantities of hyperpolarized noble gases in a continuous manner.
Nuclear magnetic resonance (NMR) is a phenomenon which can be induced through the application of energy against an atomic nucleus being held in a magnetic field. The nucleus, if it has a magnetic moment, can be aligned within an externally applied magnetic field. This alignment can then be transiently disturbed by application of a short burst of radio frequency energy to the system. The resulting disturbance of the nucleus manifests as a measurable resonance or wobble of the nucleus relative to the external field.
For any nucleus to interact with an external field, however, the nucleus must have a magnetic moment, i.e., non-zero spin. Experimental nuclear magnetic resonance techniques are, therefore, limited to study of those target samples which include a significant proportion of nuclei exhibiting non-zero spin. A highly preferred such nucleus is the proton .sup.1 H), which is typically studied by observing and manipulating the behavior of water protons (.sup.1 H.sub.2 O) in magnetic fields. Other nuclei, including certain noble gas nuclei such as .sup.3 He and .sup.129 Xe, are in principle suited to study via NMR. However, the low relative natural abundance of these isotopes, their small magnetic moments, and other physical factors have made NMR study of these nuclei difficult if not impossible to accomplish.
One important consideration in studying noble gas nuclei via NMR is that they normally yield only a very low NMR signal intensity. It is known, however, that the spin polarization of such noble gases as .sup.3 He and .sup.129 Xe can be increased over natural levels, i.e., populations of these isotopes can be artificially "hyperpolarized", to provide a much larger NMR signal. One preferred hyperpolarization technique is known as spin exchange hyperpolarization. Without describing this technique in exhaustive detail, in this scenario a noble gas is hyperpolarized via interaction with an alkali-metal vapor, such as rubidium, which itself has been polarized by absorption of laser energy of an appropriate wavelength. The polarized rubidium transfers its polarization to the noble gas through a phenomenon known as spin exchange transfer. The end result is that the noble gas becomes "hyperpolarized", i.e., more polarized than it would otherwise be. Details of the theory underlying the spin exchange hyperpolarization technique are available in the literature.
While well established as a theoretical phenomenon, the actual practice of spin exchange hyperpolarization has proven to be something of an art. The production and handling of hyperpolarized noble gases is not only logistically difficult, it is expensive as well. Moreover, due to the experimental nature of spin exchange studies, the production of hyperpolarized noble gases has typically been undertaken only on a small scale. Exquisite craftsmanship is typically required, involving expertise in a variety of fields including lasers, electronics, glass-blowing, ultra-high vacuum pump operation, high-purity gas handling as well as nuclear magnetic resonance spectroscopy.
For example, the production of a single sample of hyperpolarized noble gas has typically involved the fabrication of a single-use sealed glass cell with a volume capacity of only a few tens to a few hundred cubic centimeters. Such cells have required delicacy in manufacture, yet their quality, as measured by their tendency to depolarize the noble gas, has not always been predictable. Moreover, use of such cells for spin exchange requires that they be sealed with the alkali metal present therein. This has meant that care must be taken to remove impurities which can cause oxidation of the metal and consequent ruination of the cell. Other problems arise in the glass itself which can depolarize the noble gas faster than it can be polarized. For study of polarized noble gas by nuclear magnetic resonance (NMR) techniques, the sealed cell must be opened or destroyed to release the hyperpolarized gas into the NMR spectrometer. Proceeding to the next sample has required repeating all of these steps, including fabricating and filling a new glass cell, which might or might not have similar qualities, resulting in a tedious and often unpredictable procedure.
Middleton established for the first time the possibility of making sealed cells capable of containing larger quantities of a noble gas for hyperpolarization by the spin exchange technique. Middleton H., The Spin Structure of the Neutron Determined Using a Polarized .sup.3 He Target, Ph.D. Dissertation, Princeton University, (1994). Even so, the reliability of the procedures described in this publication has not proven to be suited to routine use, in that sample-to-sample variability has remained a problem. Moreover, there is no disclosure in this document of any method of making refillable cells or cells which could be used on a continuous or flowing basis without significant rehabilitation. Accordingly, while progress in cell manufacture has occurred, the art has not provided means for making refillable or continuous flow spin exchange pumping cells.
A publication by Becker et al., Nucl. Inst. & Meth. in Phys. Res. A, 346:45-51 (1994) describes a method for producing hyperpolarized .sup.3 He by a distinctly different polarization method known as metastability exchange. This approach requires the use of extremely low pressures of .sup.3 He, i.e., about 0.001 atm to about 0.01 atm, and does not involve the use of an alkali metal. Significant accumulation of hyperpolarized gas is limited by the necessity of using huge pumping cells (i.e., about 1 meter long) and then compressing the gas to a useful level. The Becker et al. publication discloses an ingenious but technically difficult approach which employs large volume compressors made of titanium for compressing the gas to about atmospheric pressure. Unfortunately, manufacture and operation of such a system requires great engineering skill, limiting the reproducibility and operability of the system on a routine basis. The apparatus described by Becker et al. also requires significant amounts of floor space and cannot be moved. The Becker et al. paper also avoids the use of alkali metals in the pumping cells, and does not disclose any method of producing hyperpolarized noble gas by spin exchange. Hence, the Becker et al. paper does not resolve the complexity of manufacturing pumping cells in which an alkali metal is employed. As a result, this publication does not describe or suggest any method or apparatus related to the production and delivery of arbitrarily large or small quantities of hyperpolarized noble gas by spin exchange.
It was recently demonstrated that hyperpolarized noble gases can be imaged by nuclear magnetic resonance imaging (MRI) techniques. See U.S. patent application Ser. No. 08/225,243. In addition, because the noble gases as a group are inert and non-toxic, it was found that hyperpolarized noble gases can be used for MRI of human and animal subjects. As a result, there exists a growing need for the generation of larger quantities of hyperpolarized noble gases. Moreover, because of medical and veterinary concerns, controlled uniformity and reliability in the purity of the gases and the amount of hyperpolarization have become necessary. Also, the need for convenient and reliable generation of these hyperpolarized gases has become important for use in a clinical setting in which technicians, having little or no specific training in the laboratory techniques described above, are still able to provide discrete or continuous hyperpolarized noble gas samples to subjects undergoing MRI.
In view of the above considerations, it is clear that the apparatus and methods in use in the existing art are limited in a number of ways. For example, the existing art does not provide any practical means for refilling a spin exchange polarization chamber (cell) once it has been used. Most current chambers are either permanently sealed after the first filling or have been refilled with at best unsatisfactory results. Thus, it would be of benefit to develop means for effectively refilling a pumping chamber, or even for optically pumping in a continuous flow mode in the same chamber, so as to decrease costs of materials and personnel.
Moreover, even successful fills for the permanently sealed cells used previously were accomplished via a significantly different system. In the past, an expensive ultra-high vacuum system, with either oil-free pumps or cryotrapped oil-containing pumps, has been required in order to produce a sufficiently clean apparatus for filling high quality polarization chambers. Such a system is expensive (about $30,000), not very compact (3 ft by 6 ft footprint), and requires high maintenance by a trained vacuum technician. A new system, requiring only minimal maintenance and capable of being operated without specialized knowledge of vacuum technology, would be desirable. Also, a system having a more convenient size would be useful in clinical settings.
In addition, there has been no practical way to produce hyperpolarized gas in a continuous fashion. For each spin exchange hyperpolarization procedure a new sealed sample has had to be prepared and introduced into the hyperpolarization apparatus. It would, therefore, be desirable to develop a system which overcomes this limitation to provide means for continuous hyperpolarization of flowing noble gas.
Systems for producing hyperpolarized gases have also been quite bulky, typically requiring separate rooms for their installation. Such systems are not transportable. Thus, small, convenient hyperpolarizers would be advantageous. Also transportable systems would be of benefit in situations where space is a critical consideration.
Also, there has previously been no convenient way to store substantial quantities of hyperpolarized noble gases for later distribution in discrete quantities of arbitrary amount (up to liters of gas at atmospheric pressure). It would be important to overcome this limitation as well, to provide apparatus for continuous accumulation of a hyperpolarized noble gas, as well as storage and controlled release of the hyperpolarized gas on an as-needed basis, while still retaining substantial quantities of hyperpolarization.